Erythromycin is an antibiotic formed during the culturing of a strain of Streptomyces erythreus in a suitable medium as taught in U.S. Pat. No. 2,653,899. Erythromycin, which is produced in two forms, A and B, is represented by the following structure (I):
______________________________________ ##STR3## (I) ERYTHROMYCIN Erythromycin R ______________________________________ A OH B H ______________________________________
The structure reveals that the antibiotic is comprised of three main portions: a sugar fragment known as cladinose, a second sugar moiety containing a basic amino substituent known as desosamine and a fourteen membered lactone ring referred to as erythronolide A or B or as the macrolide ring. Azithromycin is the U.S.A.N. (generic name) for 9a-aza-9a-methyl-9-deoxo-9a-homoerythromycin A, a broad spectrum antibacterial compound derived from erythromycin A. Azithromycin was independently discovered by Bright, U.S. Pat. No. 4,474,768 and Kobrehel et al., U.S. Pat. No. 4,517,359, both of which are herein incorporated by reference, and was named N-methyl-11-aza-10-deoxo-10-dihydro-erythromycin A in these patents. It has the following structure (II) wherein the numbering system conventionally employed is shown: ##STR4## The above patents also disclose that (II) and certain derivatives thereof possess antibacterial properties.
European Patent Applications 0508699A1, 0503932A1, and 0503949A1 (Merck & Co. Inc.) relate to 9-deoxo-8a-aza-8a-homoerythromycin A derivatives, including those having the formula ##STR5## wherein R is hydrogen, substituted or unsubstituted (C.sub.1 -C.sub.10)alkyl, (C.sub.2 -C.sub.10)alkenyl, or arylsulfonyl, and (among other values) one of R' and R" is hydrogen and the other is selected from hydroxyl, aralkylcarbonyloxy, amino, or amino substituted by any of (C.sub.1 -C.sub.10)alkylcarbonyl, arylcarbonyl, aryl(C.sub.1 -C.sub.10)alkylcarbonyl, (C.sub.1 -C.sub.10)alkoxycarbonyl, aryl(C.sub.1 -C.sub.10)alkoxycarbonyl, heteroarylcarbonyl, heteroarylalkylcarbonyl or arylsulfonyl, and the pharmaceutically acceptable salts and esters thereof.